Voltage clamp experiments are employed to determine the functional and structural characteristics of ionic channels in the squid giant axon. Information concerning these characteristics of the ionic channels is gained by studying the interaction of ions which block the passage of normal charge carriers and by studying the effect of voltage upon the opening and closing ("gating") of channels. The sodium conductance was isolated by the use of potassium-free solutions and voltage-clamped with pulses containing three levels of depolarization. The conductance rapidly changed during certain repolarizing clamp steps in the gating range. The percentage change in conductance increased with time of depolarization from about 0 to about 25-30% at 7 ms for a potential step from +70 to -30 mV. Conductance steps were also observed for voltage steps from various depolarized levels to -70 mV. All observed shifts were in the direction of a decreased conductance. The conductance steps appear to be a weak function of the concentration of external calcium, which also acts as a voltage-dependent channel blocker for inwardly directed sodium currents. These results suggested a voltage- and time-dependent molecular process that does not itself yield open or closed channel conformations, but that affects the magnitude of the rate constants that do connect open and closed state conformations. The technique of "voltage-activated-resonance" in nerve membranes is being developed for the purpose of resolving gating (or asymmetry) currents into components corresponding to individual voltage-sensitive molecular transitions. The forcing functions are sinusoidal changes in the electric field generated by a voltage clamp. The output is the asymmetry current component of the dielectric displacement current that is generated at the stimulus frequency, f. For sufficiently large voltage amplitudes the "global" gating kinetics are set into periodic motion whose non-linear response (expressed as harmonic content) depends on kinetic feedback patterns generated by the molecular gating process. The actual gating process will thus be determined by a comparison with model simulations.